The purpose of this project is to develop clinically useful methods of inhibiting epiretinal membrane formation and contraction. We have developed a reproducible animal model of epiretinal membrane formation and traction retinal detachment in the aphakic, vitrectomized rabbit eye injected with tissue cultured retinal pigment epithelial cells. Repeated intraocular injection of 5-fluorouracil is capable of inhibiting traction retinal detachment. Nonetheless, reversible toxicity to the photoreceptor outer segments results from 5-FU at the present dosage. Further studies in the aphakic vitrectomized eye injected with tissue cultured cells are needed to accomplish the following goals: 1. Indentify clinically useful means of sustained and targeted delivery of antiproliferative drugs to the epiretinal cells including (a) incorporation into liposomes, (b) incorporation into antibody targeted liposoms, (c) incorporation no vitreous substitutes such as sodium hyaluronate, and (d) intraocular and subconjunctival injection. 2. Identify the role of (a) irradiation and (b) irradiation combined with chemotherapy in inhibiting epiretinal membrane formation and contraction. 3. Indentify other drugs capable of inhibiting epiretinal cellular proliferation and contraction. 4. Identify the ocular toxicity of effective antiproliferative drugs. Epiretinal membrane formation and contraction remains the single most important obstacle to long-term retinal reattachment following penetrating ocular trauma and rhegmatogenous retinal detachment. A clinically useful method for inhibiting the formation and contraction of epiretinal membranes will prevent blindness in a large number of eyes that are presently lost to this complication.